Synthesis and antiplasmodial evaluation of 1H-1,2,3-triazole grafted 4-aminoquinoline-benzoxaborole hybrids and benzoxaborole analogues

A library of 1H-1,2,3-triazole-tethered 4-aminoquinoline-benzoxaborole hybrids as well as aryl substituted benzoxaborole analogues was synthesized and screened for their anti-plasmodial efficacy against both chloroquine-susceptibility 3D7 and chloroquine-resistant W2 strains of P. falciparum. The inclusion of quinoline core among the synthesized analogues resulted in substantial enhancement of anti-plasmodial activities. Further, the spacer of a flexible alkyl chain is marginally preferred over piperazyl-ethyl in inhibiting growth of P. falciparum. The most potent 4-aminoquinoline-benzoxaborole conjugate with ethyl as spacer exhibited IC50 values of 4.15 and 3.78 ?M against 3D7 CQ-susceptible and W2 CQ-resistant strains of P. falciparum with lower cross resistance with Chloroquine. There was no difference in anti-plasmodial activities between the CQsusceptible 3D7 and CQ-resistant W2 strains of P. falciparum for the benzoxaborole derivatives lacking a quinoline core.

Automated summary

A library of 1H-1,2,3-triazole-tethered 4-aminoquinoline-benzoxaborole hybrids was synthesized and screened for anti-plasmodial efficacy, with the inclusion of quinoline core resulting in enhanced activities. The most potent conjugate exhibited lower cross resistance with Chloroquine against both chloroquine-susceptible 3D7 and chloroquine-resistant W2 strains of P. falciparum.